Department of Surgery, Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA.
Human Immunology and Immunopathology, Inserm UMR 976, Université de Paris, Paris, France.
Transplantation. 2021 Nov 1;105(11):e168-e180. doi: 10.1097/TP.0000000000003776.
Humoral allogeneic immunity driven by anti-HLA donor-specific antibodies and antibody-mediated rejection (AMR) significantly impede prolonged survival of organ allografts after transplantation. Although the importance of T follicular helper (TFH) cells in controlling antibody responses has been long established, their role in directing donor-specific antibody generation leading to AMR was only recently appreciated in the clinical setting of organ transplantation. In this review, we provide a comprehensive summary of the current knowledge on the biology of human TFH cells as well as their circulating counterparts and describe their pivotal role in driving humoral alloimmunity. In addition, we discuss the intrinsic effects of current induction therapies and maintenance immunosuppressive drugs as well as of biotherapies on TFH cells and provide future directions and novel opportunities of biotherapeutic targeting of TFH cells that have the potential of bringing the prophylactic and curative treatments of AMR toward personalized and precision medicine.
体液性同种异体免疫由抗 HLA 供体特异性抗体和抗体介导的排斥反应 (AMR) 驱动，这极大地阻碍了移植后器官移植物的长期存活。尽管 T 滤泡辅助 (TFH) 细胞在控制抗体反应中的重要性早已确立，但在器官移植的临床环境中，它们在指导导致 AMR 的供体特异性抗体产生中的作用直到最近才被认识到。在这篇综述中，我们全面总结了人类 TFH 细胞及其循环对应物的生物学知识，并描述了它们在驱动体液性同种异体免疫中的关键作用。此外，我们还讨论了当前诱导治疗和维持免疫抑制药物以及生物疗法对 TFH 细胞的内在影响，并提供了针对 TFH 细胞的生物治疗靶向的未来方向和新机会，有可能将 AMR 的预防性和治疗性治疗推向个体化和精准医学。
